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[17] Lee PH, Song JK, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO trial. J Am Coll Cardiol 2018;71:
2335e42.
[18] Mojadidi MK, Elgendy AY, Elgendy IY, et al. Transcatheterpatent foramen ovale closure after cryptogenic stroke: an updated meta-analysis of
randomized trials. JACC Cardiovasc Interv 2017;10:2228e30.
[19] Shah R, Nayyar M, Jovin IS, et al. Device closure versus medical therapy alone for patent foramen ovale in patients with cryptogenic stroke: a
systematic review and meta-analysis. Ann Intern Med 2018;168:335e42.
[20] De Rosa S, Sievert H, Sabatino J, Polimeni A, Sorrentino S, Indolfi C. Percutaneous closure versus medical treatment in stroke patients with
patent foramen ovale: a systematic review and meta-analysis. Ann Intern Med 2018;168:343e50.
[21] Garg L, Haleem A, Varade S, et al. Patent foramen ovale closure in the setting of cryptogenic stroke: a meta-analysis of five randomized trials.
J Stroke Cerebrovasc Dis 2018;27:2484e93. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.005.
[22] Ntaios G, Papavasileiou V, Sagris D, et al. Closure of patent foramen ovale versus medical therapy in patients with cryptogenic stroke or
transient ischemic attack: updated systematic review and meta-analysis. Stroke 2018;49:412e8.
[23] Vaduganathan M, Qamar A, Gupta A, et al. Patent foramen ovale closure for secondary prevention of cryptogenic stroke: updated
meta-analysis of randomized clinical trials. Am J Med 2018;131:575e7.
[24] Mojadidi MK, Mahmoud AN, Patel NK, Elgendy IY, Meier B. Cryptogenic stroke and patent foramen ovale: Ready for Prime Time? J Am Coll
Cardiol 2018;72:1182e4.
[25] Mojadidi MK, Elgendy AY, Elgendy IY, Mahmoud AN, Meier B. Atrial fibrillation after percutaneous patent foramen ovale closure. Am J
Cardiol 2018;72:1183e5.
[26] Staubach S, Steinberg DH, Zimmermann W, et al. New onset atrial fibrillation after patent foramen ovale closure. Cathet Cardiovasc Interv
2009;74:889e95.
[27] Mojadidi MK, Christia P, Salamon J, et al. Patent foramen ovale: unanswered questions. Eur J Intern Med 2015;26:743e51.
[28] Mojadidi MK, Gevorgyan R, Tobis JM. In: Amin Z, Tobis J, Sievert H, Carroll J, editors. Device closure of patent foramen ovale or medical
therapy for cryptogenic stroke: the CLOSURE I trial, Chapter 22, Patent Foramen Ovale. London, UK: Springer; 2015. p. 173e9.
[29] Matsumura K, Gevorgyan R, Mangels D, Masoomi R, Mojadidi MK, Tobis J. Comparison of residual shunt rates in five devices used to treat
patent foramen ovale. Cathet Cardiovasc Interv 2014;84:455e63.
[30] Xu HB, Zhang H, Qin Y, et al. Patent foramen ovale closure versus medical therapy for cryptogenic stroke: an updated meta-analysis. J Neurol
Sci 2018;390:139e49.
[31] Riaz H, Khan MS, Schenone AL, Waheed AA, Khan AR, Krasuski RA. Transcatheter closure of patent foramen ovale following cryptogenic
stroke: an updated meta-analysis of randomized controlled trials. Am Heart J 2018;199:44e50.
[32] Ahmad Y, Howard JP, Arnold A, et al. Patent foramen ovale closure vs. medical therapy for cryptogenic stroke: a meta-analysis of random-
ized controlled trials. Eur Heart J 2018;39:1638e49.
[33] Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med June 26, 2014;370(26):2467e77.
[34] Sanna T, Diener H-C, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014;370:2478e86.
[35] Kent DM, Dahabreh IJ, Ruthazer R, et al. Device closure of patent foramen ovale after stroke: pooled analysis of completed randomized trials.
J Am Coll Cardiol 2016;67:907e17.
[36] FDA approval Amplatzer Occluder Device. https://www.accessdata.fda.gov/cdrh_docs/pdf12/p120021d.pdf. Last Accessed June 30,2018.
[37] FDA Approval For Gore Cardioform Septal Occluder. https://www.accessdata.fda.gov/cdrh_docs/pdf5/P050006s060a.pdf. Last Accessed
June 30,2018.
[38] Collado FMS, Poulin MF, Murphy JJ, Jneid H, Kavinsky CJ. Patent foramen ovale closure for stroke prevention and other disorders. J Am
Heart Assoc 2018;7:e007146.
[39] Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a
guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:2160e236.
[40] Wein T, Lindsay MP, Cote R, et al. Canadian stroke best practice recommendations: secondary prevention of stroke, sixth edition practice
guidelines, update 2017. Int J Stroke 2018;13:420e43.
[41] Leitlinien fu
¨
r Diagnostik_und_Therapie_in der_Neurologie_©DGN. 2018. https://www.dgn.org/46-startseite/3642-ende-des-patts-
kardiologen-und-neurologen-empfehlen-pfo-verschluss-zum-schutz-vor-schlaganfall.
[42] Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008;25:457
e507.
[43] Thaler DE, Di Angelantonio E, Di Tullio MR, et al. The risk of paradoxical embolism (RoPE) study: initial description of the completed
database. Int J Stroke 2013;8:612e9.
[44] Smith EE, Saposnik G, Biessels GJ, et al. Prevention of stroke in patients with silent cerebrovascular disease: a scientific statement for
healthcare professionals from the American heart association/American stroke association. Stroke 2017;48:e44e71.
[45] Bernick C, Kuller L, Dulberg C, et al. Silent MRI infarcts and the risk of future stroke: the cardiovascular health study. Neurology 2001;57:
1222e9.
[46] Mojadidi MK, Mahmoud AN, Elgendy IY. Percutaneous patent foramen ovale closure for cryptogenic stroke: learning from clinical trial and
error. J Thorac Dis 2017;9:4222e5.
[47] Mojadidi MK, Zaman MO, Elgendy IY, et al. Cryptogenic stroke and patent foramen ovale. J Am Coll Cardiol 2018;71:1035e43.
[48] Zaman MO, Patel NK, Mojadidi MK. Patent foramen ovale closure for patients excluded from the randomized cryptogenic stroke trials. Clin
Res Cardiol 2018;107:1187e8.
[49] Mazzucco S, Li L, Binney L, Rothwell PM. Prevalence of patent foramen ovale in cryptogenic transient ischaemic attack and non-disabling
stroke at older ages: a population-based study, systematic review, and meta-analysis. Lancet Neurol 2018;17:609e17.
[50] Kent DM, Dahabreh IJ, Ruthazer R, et al. Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale:
an individual participant data meta-analysis. Eur Heart J 2015;36:2381e9.
[51] Mojadidi MK, Zaman MO, Patel NK. Letter by mojadidi et al regarding article, “closure of patent foramen ovale versus medical therapy in
patients with cryptogenic stroke or transient ischemic attack: updated systematic review and meta-analysis”. Stroke 2018;49:e212.
[52] Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med
2001;345:1444e51.
III. STROKE AND PFO
7. NEWER RANDOMIZED TRIALS OF PFO CLOSURE FOR STROKE (CLOSE, REDUCE AND DEFENSE-PFO)90
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[53] Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med 2018;378:
2191e201.
[54] TCTMD. Dabigatran Trials Come Up Short for Stroke of Unknown Cause and Cerebral Venous Thrombosis. https://www.tctmd.com/news/
dabigatran-trials-come-short-stroke-unknown-cause-and-cerebral-venous-thrombosis.
[55] Homma S, Sacco RL, Di Tullio MR, et al. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in
Cryptogenic Stroke Study. Circulation 2002;105:2625e31.
[56] Kasner SE, Swaminathan B, Lavados P, et al. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source:
a prespecified subgroup analysis from the NAVIGATE ESUS trial. Lancet Neurol 2018;17:1053e60.
[57] Mir H, Siemieniuk RAC, Ge LC, et al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation in patients with patent foramen
ovale and cryptogenic stroke: a systematic review and network meta-analysis incorporating complementary external evidence. BMJ Open
2018;8:e023761.
[58] Kuijpers T, Spencer FA, Siemieniuk RAC, et al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for
management of cryptogenic stroke? A clinical practice guideline. BMJ 2018;362:k2515.
III. STROKE AND PFO
REFERENCES 91
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CHAPTER
8
Myocardial Infarction and PFO
Jonas Dominik Ha
¨
ner, Bernhard Meier
University Hospital Bern, Bern, Switzerland
OUTLINE
Introduction 95
Prevalence of Embolic Myocardial Infarction 96
Causes of Embolic Myocardial Infarction 96
Frequency of Paradoxical Coronary Embolism 97
Evidence for Etiologic Association of the PFO and
Embolic Myocardial Infarctions 99
Prevalence of PFO in Acute Coronary Syndrome
Patients 100
Incidence of Myocardial Infarction in Patients
with a PFO 101
Risk of Myocardial Infarction in Patients With
Venous Thromboembolism
101
Differential Diagnosis
103
Management of Patients With Myocardial Infarction
Attributable to Paradoxical Coronary Embolism
105
Secondary Prevention After Paradoxical Embolic
Myocardial Infarction in the Presence of a PFO
106
Conclusions
107
References
107
INTRODUCTION
The patent foramen ovale (PFO) represents a potential cause of a myocardial infarction (MI) in PFO carriers, i.e.,
about every fourth person. One explanation for the decreasing prevalence of PFO with age [1] is selective mortality
for which MI by paradoxical embolism could be co-responsible. The selective mortality hypothesis is supported by a
retrospective study of Konstantinides et al., which found a PFO to be an independent predictor of mortality in
patients with pulmonary embolism, presumably from paradoxical embolism to the cerebral and peripheral
(coronary) circulations [2]. Likewise, the significantly increased morta lity shown in a long-term comparative
follow-up study of PFO carriers randomly slated for PFO closure or medical therapy after an index cerebral event
corroborates an increased mortality associated with a PFO after an index event [3].
Similar to paradoxical embolism-mediated MI, stroke by paradoxical embolism is also significantly underesti-
mated. The annual risk of a stroke in people with a PFO is reported at only 0.1% [4] because PFO is only considered
as a cause of stroke if all other causes are excluded, i.e., in so-called cryptogenic strokes. This is counterintuitive
because, in absolute numbers, PFO likely causes more strokes and MIs in older and sicker patients (where
there are more venous thrombosis and more Valsalva maneuvers due to respiration, defecation, and micturition
problems).
Missing the diagnosis of a PFO responsible for coronary embolism in patients with MI significantly jeopardizes
adequate treatment. PFO closure is a simple and safe intervention and provides lifelong protection (mechanical
vaccination [5]) against PFO-mediated paradoxical embolism. PFO closure is effective and simultaneously allows
prevention of MI and stroke [6e8], although no randomized study was designed or sufficiently powered to prove
95
PFO Closure for Stroke, Myocardial Infarction, Peripheral Embolism, Migraine, and Hypoxemia
Copyright © 2020 Elsevier Inc. All rights reserved.https://doi.org/10.1016/B978-0-12-816966-7.00008-7
https://t.me/med1917
this so far. On the other hand, medical treatment cannot assure protection from paradoxical embolism to a similar
degree at comparable risk. Antiplatelet agents, which are usually given after MI, do not sufficiently prevent para-
doxical embolism as shown in the stroke trials [6,8]. Oral anticoagulants, an accepted treatment option in coronary
embolism from other causes (e.g., atrial fibrillation, thrombophilia), are prone to poor compliance [9] and reduced
efficacy in some conditions like malignancies, and they carry a substantial cumulative annual bleeding risk.
Finally, patients with paradoxical embolism-mediated MI who have no risk for atherosclerosis may inappropri-
ately be recommended to take unnecessary preventive drugs, like antiplatelets or cholesterol-lowering medications,
for no good reason and for the rest of their lives. Therefore, even though PFO closure has not specifically been stud-
ied in paradoxical coronary embolism, it should be used to prevent potentially life-threatening recurrent events such
as another MI or a cerebral event (a collateral benefit). The topic of PFO and noncoronary peripheral embolism is
discussed in Chapter 9.
Prevalence of Embolic Myocardial Infarction
The prevalence of coronary embolism responsible for MI varies between investigated populations and applied
methods. In an autopsy study, Prizel et al. fo und thrombotic material in the absence of acute plaque rupture in
13% of acute MI cases, due to a presumed embolic source [10]. This could be overestimated as some thrombi
may have been generated in situ by undetectable plaque erosions. At the other extreme, a retrospective angiography
study of 1776 consecutive patients with a first acute coronary syndrome attributed 2.9% to coronary embolism.
This study underestimates the incidence because the possibility of an embolic MI was excluded by definition in pa-
tients with atherosclerotic stenosis 25% in any major epicardial coronary artery [11]. Taking into account that pa-
tients with some degree of coronary artery disease do not only have a higher risk for plaque rupture but also for
thromboembolism (atrial fibrillation, smoking, age, or other comorbidities), coronary embolism is to be expected
more frequently in this population than in young and healthy people.
Atrial fibrillation is considered the most common reason for embolic MI but, like for PFO, its causal frequency is
underestimated. The presence of atherosclerosis is frequent in patients with atrial fibr illation and makes cardiolo-
gists forget the possibility of embolic coronary obstruction. PFO as a cause for embolic MI is even more discounted
than atrial fibrillation, both in clinical practice and in research studies. Instead of regarding coronary embolism as a
diagnosis of exclusion, it should be considered in the differential diagnosis of all patients with a coronary obstruction
looking even remotely embolic, particularly if there is a condition predisposing to paradoxical embolism. This has
been proposed by Charles et al. already in 1983 [12].
Causes of Embolic Myocardial Infarction
Coronary embolism is possible by 3 mechanisms: direct, parado xical, or iatrogenic [13]. Direct coronary embolism
results from a thrombus originating distal to the pulmonary capillary bed from pulmonary veins, left atrium (espe-
cially left atrial appendage in the setting of atrial fibrillation), mitral valve, left ventricle, aortic valve, or sinus of Val-
salva. Atrial fibrillation is the most common presumptive culprit in patients with assumed or documented coronary
embolism (28%e73% of embolic MIs), followed by dilated cardiomyopathy (10%e25%), infectious endocarditis (4%
e8%), other valvular heart disease (0%e15%), intracardiac neoplasia (e.g., myxoma; 0%e6%), or marantic (nonin-
fectious) endocarditis in patients with malignancy. Coronary embolism is also attributed to prothrombotic condi-
tions that may promote thrombus/embolus formation within the arterial system, such as systemic autoimmune
disease and malignancies (Table 8.1 ) [11,14]. However, the presence of coronary artery disease was illogically consid-
ered to exclude embolism as a potential cause in most studies, the result being a gross underestimation of this entity.
Paradoxical em bolism requires an unfiltered passage bet ween the right and left circulations. Although PFO is the
most frequent route of an embolus to cross over from the venous to the syst emic arterial circulations, other paths
must also be considered. Any atrial shunt, such as all types of atrial septal defects, can enable paradoxical embolism
during moments of transiently increased right heart pressures in the presence of thrombus material. Ventricular
septal defects almost never allow right to left shunts, unless Eisenmenger’s syndrome is present. Neither does a pat-
ent ductus arteriosus, which, in addition, cannot embolize to the coronary or cerebral arteries, save the rare ductus
that inserts proximal to the left subclavian artery feeding the left vertebral artery. Finally, paradoxical coronary em-
bolism can occur via pulmonary arteriovenous fistulae [15].
8. MYOCARDIAL INFARCTION AND PFO96
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A further common cause of coronary embolism is iatrogenic dislocation of thrombotic or calcific material with
embolization to the distal coronary circulation during cardiac interventions (e.g., cardiothoracic surgery, coronary
angiography and intervention, or percutaneous valvular interventions) [16].
FREQUENCY OF PARADOXICAL CORONARY EMBOLISM
The ratio of resting coronary to cerebral blood flow is approximately 1:3 (225 vs. 750 mL per minute). However,
both paradoxical and direct embolic MI are seldom diagnosed in clinical practice or published in the literature, far
from a 1:3 ratio compared to strokes. The factors listed below must be considered but cannot completely explain this
discrepancy.
Emboli passing the aortic valve may preferentially wind up in the distal systemic or cerebral circulations because
of a relatively linear trajectory from the left ventricular outflow tract. The coronary ostia may be relatively protected
from embolic events [13]. From autopsy studies, we know that the clinical consequences of coronary embolism
depend on the size of the embolus, size of the affected artery, presence of a collateral circulation, and viability of
the affected myocardium. A large embolus usually occludes a major coronary artery proximally or even at the
ostium [17] with subsequent acute and widespread myocardial ischemia, resulting in myocardial necrosis or fatal
arrhythmia. Smaller emboli impact more distally, leading to a limited epicardial infarction. Collateral blood flow
is commonly absent if a previously widely patent vessel is abruptly closed by an embolus, in contrast to a vessel
progressively obstructed by atherosclerosis over time. In people with coronary artery disease, an embolus typically
closes the vessel at a tight stenosis. In these cases, collaterals are often present and protective, and the event may
remain asymptomatic. In the brain, collaterals also play a major role, albeit only in proximal obstructions, and
some brain areas show no clinical signs in case of small infarctions. Cerebral symptoms are, however, taken more
seriously than chest pain. This tilts the sca le toward embolic strokes that are diagnosed more reliably than MIs
that occur by an embolic mechanism.
The actual prevalence of MI caused by paradoxical embolism is difficult to estimate, mainly because a PFO is
rarely searched for, especially when other possible causes of MI are present. Yet, paradoxical coronary embolism
can be found in patients at all stages of life, very rarely in children [18], but frequently in the elderly (Fig. 8.1). Similar
TABLE 8.1 Causes of Coronary Embolism.
Causes
Percent of Noniatrogenic Coronary Embolism
Shibata et al. 2015
a
[11] Popovic et al. 2018
b
[14]
Direct coronary embolism
Atrial fibrillation 73% 29%
Cardiomyopathy (mainly DCM/HCM) 25% 5%
Intracardiac tumor 6%
Valvular heart disease 19% 12%
Mitral or aortic valve stenosis 5% 0%
Prosthetic heart valve 5% 4%
Infective endocarditis 4% 8%
Malignancy 15%
Hematologic disorder (APS) 8%
Paradoxical coronary embolism 4% 2%
Undetermined cause 8% 26%
Iatrogenic coronary embolism
APS, antiphospholipid syndrome; DCM, idiopathic dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy.
a
In 52 (2.9%) of 1776 patients first myocardial infarction was related to coronary embolism.
b
In 53 (4.3%) of 1232 patients myocardial infarction was related to coronary embolism.
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
FREQUENCY OF PARADOXICAL CORONARY EMBOLISM 97
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to PFO-mediated stroke, the diagnosis remains presumptive in most cases because it is difficult to prove that the
MI was caused by a paradoxical embolism. Furthermore, embolic MIs, especially if small, may be asymptomatic
or neglected, and therefore remain undetected.
A summary of older autopsy studies reported paradoxical embolism to be responsible for 3.4% of lethal embolic
MIs [12]. No clinical study of patients with acute MI exclusively focused on paradoxical coronary embolism.
However, some retrospective cohort studies assessed the incidence of coronary embolism of any cause in patients
with ST-segment elevation MI (STEMI). In a cohort of 1232 STEMI patients between 2006 and 2015, 53 (4.3%)
were considered of embolic cause based on a retrospective review of angiograms [14]. Of these, only 1 case (2%
of embolic causes, <0.1% of all MIs) was attributed to paradoxical embolism in the presence of a PFO. Among
factors that may result in intracardiac or valvular thrombosis and embolism, atrial fibrillation was the predominant
explanation for coronary embolism (28%), followed by dilated cardiomyopathy (9%), endocarditis (8%), and
intracardiac tumor (6%). Of note, in 14 patients (26%), no explanation for coronary embolism was found and in
another 10 patients (19%), the underlying cause was presumed to be a systemic disorder such as autoimmune dis-
ease (e.g., antiphospholipid syndrome) or malignancy, both of which frequently predispose to venous thromboem-
bolism. Paradoxical embolism through a PFO should have been a consideration in most of these patients. However,
(A)
(B)
(F)
(G)
(D)
(E)
(C)
FIGURE 8.1 Myocardial infarction (MI) due to PFO in an elderly patient. An 86-year-old woman presented with acute anterior MI and
concomitant pulmonary embolism 2 days after elective surgery (hysterectomy). Coronary angiography showed nonsignificant atherosclerotic
coronary stenoses in the proximal left anterior descending coronary artery (LAD, A, thin arrows) and a saddle thrombus in the bifurcation of the
mid-LAD and first diagonal branch (A, bold arrows). The obstruction was successfully treated with thrombus aspiration only and final angiography
showed good distal blood flow (B) Macroscopically, the aspirated thrombus had 2 bodies connected by a thin filament (C), exactly corresponding
to the aspect on the angiogram (A) The presence of atherosclerosis is erroneously and frequently considered to exclude an embolic cause of
coronary obstruction; in the setting of concomitant pulmonary embolism (D, computed tomography angiography, arrow), paradoxical embolism
was assumed as the cause of the MI and corroborated by detection of a PFO during right heart catheterization at the index intervention (E) The
PFO was immediately closed with a 25 mm Amplatzer PFO Occluder (F and G), without any echocardiographic documentation or guidance, to
prevent further cardiac, cerebral, or other systemic paradoxical embolic ischemic events.
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
8. MYOCARDIAL INFARCTION AND PFO98
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only 3 of the 14 patients with unknown cause and none of the patients with an autoimmune disorder or malignancy
underwent screening for a PFO with transesophageal echocardiography (TEE). This lack of suspicion for PFO under-
estimated the etiology of paradoxical coronary embolism in this retrospective cohort study.
Similarly, in a cohort study of 1776 consecutive Japanese patients with a first acute MI between 2001 and 2013,
only 2 among 52 patients with embolic MI (4% of embolic causes, 0.11% of all MIs) were assumed to have suffered
paradoxical embolism from a deep vein thrombosis through an atrial septal defect. TEE, however, was performed
only in half of the cohort [11], again indicating that in clinical practice, the threshold is very high to consider
paradoxical embolism and to search for a PFO, even in patients where the MI is considered embolic. In both
studies, patients with any coronary artery stenosis 25%wereexcluded,ignoringthatcoronaryarterydisease
and (paradoxical) coronary embolism may occur concomita ntly, and atherosclerosis even begets thromboembo-
lism (Fig. 8.1).
Another study reviewed the indications of 416 patients referred for PFO closure. Only 12 (2.9%) were due
to systemic embolism, with acute MI in 8 of those (1.9% of total population) [19]. More than half of the pa-
tients with systemic embolism had a history of previous cerebrovascular events, a constellation that may have
lowered the threshold to consider paradoxical embolism as the mechanism of the ischemic event and to search
for the PFO.
In an imaging study, Wo
¨
hrle et al. performed cardiac magnetic resonance imaging, including late gadolinium
enhancement analysis, in 74 patients with PFO and so-called cryptogenic stroke but without a history of MI, to
detect subclinical MIs [20]. They found transmural or subendocardial late gadolinium enhan cement in 8 patients
(10.8%). In 7 of them, coronary artery disease was ruled out by coronary angiography. The transmural or
subendocardial pattern of late gadolinium enhancement is typical for myocardial scar due to MI, most probably
from an embolic cause, particularly given the absence of obstructive coronary artery disease in most patients.
Furthermore, the relatively small extent of late gadolinium enhancement (mean late gadolinium enhancement
was 7.9 2.4% of left ventricular muscle mass) led the authors to postulate PFO-mediated paradoxical embolism
of small thrombotic masses as the main culprit in th ese patients. Therefore, this study demonstrated the presence of
concomitant asymptomatic or subclinical, presumably paradoxical embolic MI in approximately every 10th patient
with so-called cryptogenic stroke and PFO with a low burden of cardiovascular risk factors. Unfortunately, this
study lacked a control group.
In a study assessing the presence of late gadolinium enhancement between 152 master athletes (54.4 8.5 years)
and 92 controls of similar age, sex, and low cardiovascular risk profile, suben docardial late gadolinium enhancement
was found in a substantially lower proportion of participants [21]. In only 8 athletes (5.2%) and in none of the
controls, late gadolinium enhancement was seen. Of interest, significant coronary artery disease was only found
in 38% of the athletes with evident MI, while the cause was not further evaluated in the other 62%. Given the
high prevalence of PFO in the general population and the increased risk of venous thromboembolism in athletes
due to exertion-related dehydration and frequent Valsalva maneuvers during certain exercises, paradoxical
embolism may be the mechanism of subclinical MI without coronary artery disease in at least some of the athletes.
EVIDENCE FOR ETIOLOGIC ASSOCIATION OF THE PFO AND EMBOLIC MYOCARDIAL
INFARCTIONS
Several case reports describe patients with a PFO who had a simultaneous pulmonary embolism and embolic
MI [17,22]. The concomitant occurrence of venous or pulmonary thromboembolism and MI is very suggestive of
paradoxical embolism, and it is mandatory that an evaluation for the presence of a PFO be performed. Interestingly,
a Danish study found higher rates of both stroke and MI in patients with deep venous thrombosis, and even more in
those with pulmonary embolism, which indirectly proves that thrombi have traveled through the right atrium [23].
However, neither the authors nor the accompanying editorial [24] mentioned paradoxical embolism as a plausible
explanation, allegedly because PFO was not mentioned in any of the few randomly reviewed patient charts.
More recently, in an observational study of 361 consecutive patients with acute pulmonary embolism, there was a
4-fold increased incidence of a recent ischemic stroke in patients with a PFO versus those with no PFO [25]. These
data corroborate the finding that paradoxical embolism is an important mechanism of ischemic stroke and systemic
embolism in general in patients who have a PFO [2]. Causality is suggested in situations listed in Table 8.2. Causality
is proven if the embolus is identified in the abnormal communication between the venous and arterial system, as
occasionally documented by TEE [26e29].
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
EVIDENCE FOR ETIOLOGIC ASSOCIATION OF THE PFO AND EMBOLIC MYOCARDIAL INFARCTIONS 99
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PREVALENCE OF PFO IN ACUTE CORONARY SYNDROME PATIENTS
Among patients with so-called cryptogenic stroke, the prevalence of PFO is 54%, higher than the 20% in the gen-
eral population [30]. A similarly higher rate of PFO in patients with acute MI of presumed nonatherosclerotic cause
has not yet been shown. One case-control study compared 18 patients with acute MI and angiographically normal
coronary arteries with 18 matched controls without a history of coronary artery disease. Contrast-enhanced trans-
thoracic echocardiography revealed a PFO prevalence of 28% in both groups. However, the study was limited by
the small sample size and the use of transthoracic echocardiography instead of TEE or transcranial Doppler
(TCD) [31], although the documented incidence of PFO is higher than in many TEE studies. The Young Adult
Myocardial Infarction and Ischemic Stroke study evaluated the prevalence of major venous-to-arterial shunts by
TCD after intravenous microbubble administration in young patients with MI (n ¼ 101), ischemi c stroke
(n ¼ 101), and controls (n ¼ 202). While major venous-to-arterial shunts were associated with stroke, this was not
the case for MI [32]. Shortcomings of this study were that strokes and MIs of all causes were included and
confounded the analyses.
TABLE 8.2 Risk Factors for Paradoxical Coronary Embolism in Patients With PFO.
PROTHROMBOTIC CONDITIONS
Documented/concomitant venous thrombosis or pulmonary embolism
Immobilization (after surgery, major surgery also produces hypercoagulability during illness,
long distance travel)
Thrombophilia (e.g., protein C, protein S, Leiden factor V, antiphospholipid syndrome)
History of venous thromboembolism
Familial predisposition to venous thromboembolism
Obesity
Smoking
Oral contraception containing estrogen derivates
Malignancy
(TRANSIENTLY) RAISED RIGHT ATRIAL PRESSURE
End of a sustained Valsalva maneuver
Coughing, sneezing
Defecation, micturition
Squatting, isometric exercise, diving
Sexual intercourse, orgasm
Tricuspid valve stenosis
Right heart failure, severe tricuspid valve regurgitation Life at high altitude
ANATOMICAL PREDISPOSITIONS
Large PFO
Atrial septal aneurysm
Eustachian valve
Chiari network
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
8. MYOCARDIAL INFARCTION AND PFO100
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INCIDENCE OF MYOCARDIAL INFARCTION IN PATIENTS WITH A PFO
No large-sized cohort study has assessed the incidence of acute coronary syndromes in patients with PFO. As
mentioned before, a cardiac magnetic resonance imaging study found subclinical myocardial scars in 10.8% of pa-
tients with stroke of no apparent cause other than a PFO [20].
Tabl e 8.3 summarizes the incidence of MI in the major stroke trials comparing PFO closure to medical therapy
[33e35]. In the CLOSE (PFO Closure or Anticoagulants versus Antiplatelet Therapy to Prevent Stroke Recurrence)
trial, 664 patients, who had a recent stroke attributed to PFO with an associated atrial septal aneurysm or large shunt,
were randomized to PFO closure, anticoagulation, or antiplatelet therapy; only 1 patient in this cohort had a history of
MI [6]. This low rate of baseline history of MI is probably attributable to selection bias, taking into account that all of
these patients were screened for alternative causes of stroke and prior MI was considered a sign of atherosclerosis and,
thus, an exclusion criterion. During a median follow-up of more than 5 years, not a single systemic embolic event
(including embolic MI) was detected in any group [6]; this can be explained by the preventive treatment with blood
thinners or PFO closure in these patients during the study period.
Also in the RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Cur-
rent Standard of Care Treatment) trial, which had a higher burden of cardiovascular risk factors as compared to the
CLOSE trial, only 2.9% of the 980 patients randomized to PFO closure or medical therapy had known coronary artery
disease (0.7% presenting with a history of MI) [8]. Although only recent MI (within 6 months) was a strict exclusion
criterion, it can be assumed that any history of MI put doubts on the prerequisite for inclusion of cryptogenic stroke.
Acute cardiac events (cardiac arrest or MIs), reported during a median follow-up of 5.9 years, occurred in only 13
patients (8 in the PFO closure group and 5 in the medical treatment group), again explainable by the preventive mea-
sures such as blood thinners or PFO closure imposed by the trial [8].
In the trials REDUCE (Gore Helex Septal Occluder/Gore Cardioform Septal Occluder and Antiplatelet Medical
Management for Reduction of Recurrent Stroke or Imaging-Confirmed Transient Ischemic Attack in Patients with
PFO, comparing PFO closure and antiplatelet therapy vs. antiplatelet therapy only) [7] and DEFENSE-PFO (Device
Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk PFO, comparing PFO closure and
antiplatelet or anticoagulant therapy vs. medical therapy) [34], patients with a history of MI were excluded. Cardiac
events were very rare in both studies with all patients under preventive measures. In REDUCE (664 patients with
cryptogenic stroke), only 1 cardiac arrest was reported during the median follow-up of 3.2 years [7]. Likewise, in
the DEFENSE-PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk
PFO) trial, no systemic embolism was detected during a median follow-up of 2.8 years among 120 patients with
stroke attributed to a high-risk PFO [34]. The clinical trials of PFO closure for stroke are discussed in Chapter 6
and Chapter 7.
Patients with prior coronary artery disease were also excluded from the PRIMA (Percutaneous Closure of PFO in
Migraine with Aura) [36] and PREMIUM (Percutaneous Closure of PFO in Patients With Migraine written out name
for this trial as in all other chapters) [37] both randomized trials, comparin g PFO closure to medical therapy in pa-
tients with migraine headache over 1 year (Chapter 11). These subjects were younger than the stroke cohorts and
were protected against paradoxical embolism with antiplatelets over several months in the medical arm or with
PFO closure. Strokes and MIs did not occur.
RISK OF MYOCARDIAL INFARCTION IN PATIENTS WITH VENOUS
THROMBOEMBOLISM
A Danish populationebased cohort study (mentioned above) assessed the risk of MI and stroke among patients
with deep vein thrombosis (DVT) or pulmonary embolism as compared to those without venous thromboembolism
over a 20-year period. The study found significantly higher risks for MI and stroke within the first year after the
thromboembolic event (relative risk 1.6 and 2.2 after deep vein thrombosis, 2.6 and 2.9 after pulmonary embolism,
respectively), and thereafter a 20%e40% increased risk for arterial cardiovascular events up to 20 years [23]. Para-
doxical embolism as a potential cause of the increased incidence of stroke and MI was not even mentioned in the
paper [23] or the accompanying editorial [24]. A PFO as the pathway for a paradoxical embolus in the setting of
a DVT or pulmonary embolism is much more likely as a cause of the stroke or MI than the discussed common
risk factors for arterial and venous thrombosis and similar prothrombotic mechanisms such as thrombogenesis,
endothelial damage, or inflammation. The prevalence of PFO was unfortunately not evaluated in that study. PFO
IV. NON-CEREBRAL PARADOXICAL EMBOLISM AND PFO
RISK OF MYOCARDIAL INFARCTION IN PATIENTS WITH VENOUS THROMBOEMBOLISM 101
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